The invention relates to a diagnostic procedure for the recognition of a functional disorder of the pancreas. The areas of application are medicine and the pharmaceutical industry.
Functional disorders of the pancreas may be the result of various illnesses whose diagnosis should be underpinned by the definition of functional criteria. The most frequent diseases of the pancreas are chronically recurrent and acute pancreatitis.
Chronic pancreatitis is an insidious progressive disease in which functioning pancrease tissue gradually degenerates in a scleroticising process. It is characterised by its clinical symptoms (abdominal complaints, steatorrhoea, weight loss), typical morphological changes of the gland (calcification, dilated and irregularly demarcated Ductus pancreaticus) and by a progressive exocrine and endocrine loss of function (indigestion, diabetes mellitus). The incidence of chronic pancreatitis is 6 or 8 new cases per 100 000 persons per annum in West Europe. The diagnosis of chronic pancreatitis is becoming increasingly frequent as a result of increasing alcohol consumption.
A number of functional criteria can be identified for the underpinning of clinical and morphological diagnoses. The most sensitive method of analysis is the Secretin-Caerulin or Secretin-Cholecystocinin test, which is, however, unpleasant for the patient and very time-consuming. Indirect test methods that are used include the Lundh-, NBT-PABA- and Pancreoauryl-tests. The identification of trypsin in serum or of chymotrypsin in stool is also of a certain practical significance. The disadvantage that is common to all these indirect test methods is their lack of specificity.
Of all the indirect function tests, the identification of Elastase 1 is the test with the highest sensitivity and specificity (Löser, C., Therapie & Erfolg 1997; 1:411-413). It has become established in daily practice as the standard test for exocrine pancreas function diagnostics. The basis for this test consists of polyclonal antibodies against Elastase 1 (Elastase 1-RIA, Abbott) or mono- and/or polyclonal anti-Elastase-1 antibodies, which are obtained by immunisation with an antigen containing the amino-acid sequence Thr-Met-Val-Ala-Gly-Gly Asp-Ile-Arg (SEQ ID NO: 1) or immunologically effective partial peptides of this. (EP 0 547 059 B1).
Pancreas-Elastase is a proteolytic digestion enzyme. Compared with the common parameters of pancreas diagnostics (e.g. chymotrypsin activity in stool), quantitative Elastase identification has crucial advantages. The enzyme is formed exclusively in the pancreas and displays extraordinary stability during the passage through the intestines, i.e. the concentration of Elastase reflects the secretion performance of the pancreas.
Despite its superiority to other exocrine parameters, the traditional Elastase 1-ELISA methods fail in too many cases to identify pancreas elastase, even though it is present in substantial concentrations.